An exciting possibility, raised by the recent development of light-gated channels such as channelrhodopsin, is the restoration of visual sensitivity in patients that are blind due to degeneration of rod or cone photoreceptors or the retinal pigment epithelium (RPE) cells that nourish the photoreceptors. Development of such a therapeutic approach to blinding eye disease supports the mission of the National Eye Institute, which "supports research that helps .. treat eye diseases.. and ..leads to sight-saving treatment". Photoreceptor and RPE degeneration causes blindness in many common eye diseases, such as macular degeneration, as well as in blinding exposure to lasers or other intense lights. It is likely that the approach to restoring vision studied here is feasible, as shown by recent research in which light-gated channels were inserted into retinal cells of blind rodents and produced vision. The studies proposed here will test the quality of vision that can be produced by this approach in macaque monkeys, whose vision is virtually identical to human vision. The research plan involves creating small patches of blind retina in macaque monkeys, caused by photoreceptor/RPE damage due to prolonged exposure to a 568 nm laser. Initial studies will use visual testing to verify that the light-exposed regions of retina are completely blind. The light-gated channel channelrhodopsin2 will then be inserted into undamaged retinal ganglion cells overlying the regions of photoreceptor/RPE damage by intravitreal injection of AAV2 viral vector. Psychophysical testing will then measure the restored vision mediated by the channelrhodopsin and verify that there is no residual vision for wavelengths of light beyond that absorbed by channelrhodopsin. The actual restoration of vision by insertion of light-gated switches in humans will require a gene therapy approach, in which a virus containing the light switches was injected into the eye. This is the method being used in the present study, although with macaque monkeys rather than human subjects. If this approach is successful, applications to human vision could be initiated in the near future. PUBLIC HEALTH RELEVANCE: Degeneration of photoreceptor/RPE is the cause of blindness in common eye diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), prompting a search for a visual prostheses that can provide vision mediated by the surviving inner retinal neurons. The research proposed here will examine the possibility that visual perception can be restored by this prosthesis in macaque monkeys blinded by photoreceptor/RPE degeneration.